Preservation of ischemic myocardium by a new converting enzyme inhibitor, enalaprilic acid, in acute myocardial infarction

Hock, Carl E.; Ribeiro, Lair G.T.; Lefer, Allan M.

doi:10.1016/0002-8703(85)90587-3

Cited by 90 publications

(30 citation statements)

References 14 publications

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“…A prelimi nary study from this laboratory has recently shown that trilinolein at concentration ranges from 10-10 to 10-6 AT dilated a rat aortic strip in vitro, and the relaxation effect was endo thelium-dependent [unpubl. data], A number of pharmacological substances, e.g., calcium channel blocker [16], (3-adrenoceptor-blocking agent [17], antioxidant [18], potassium channel opener [19], angiotensin-converting enzyme inhibitor [20], platelet-activating fac tor antagonist [21], prostaglandin and its ana logues and nitric oxide donor, have been shown to protect myocardium against isch emic damage or suppress ventricular arrhyth mias [22,23]. Whether the beneficial effects of trilinolein on infarct size reduction were secondary to vasodilation or/an improvement of erythrocyte deformability requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Trilinolein Reduces Infarct Size and Suppresses Ventricular Arrhythmias in Rats Subjected to Coronary Ligation

et al. 1995

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Trilinolein, a triacylglycerol with linoleic acid as the only fatty acid residue in all esterified positions of glycerol, was previously found to improve erythrocyte deformability in vitro. In this study, the in vivo antiarrhythmic and anti-ischemic effects of trilinolein in coronary ligated rats were investigated. Male Sprague-Dawley rats were anesthetized with urethane. Trilinolein, at dosages ranging from 10–¹¹ to 10^–7 g/kg, was administered intravenously 15 min before ligation of coronary artery. Also, the effect of trilinolein on arrhythmia was studied by ligating the coronary artery for 30 min, then reperfusing myocardium for 10 min. During the 30-min ischemia, trilinolein reduced not only the number of ectopic beats but also the incidence rate and duration of ventricular tachycardia. At 10–⁷ g/kg, trilinolein completely suppressed all ventricular arrhythmias. Ventricular arrhythmias during 10 min reperfusion were also reduced by trilinolein at similar dosages. Furthermore, the effect of trilinolein on infarct size was evaluated by occluding the coronary artery for 4 h before the infarct zone was stained and weighed. In rats subjected to 4 h coronary ligation, pretreatment with 10–⁷ g/kg trilinolein at 15 min prior to the coronary ligation significantly reduced infarct size. Trilinolein may protect myocardium against ischemic injury and suppress arrhythmia during ischemia and reperfusion.

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Section: Discussionmentioning

confidence: 99%

Trilinolein Reduces Infarct Size and Suppresses Ventricular Arrhythmias in Rats Subjected to Coronary Ligation

et al. 1995

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“…However, several experiments suggest that the anti-ischaemic effect of the sulphydryl-containing ACEI captopril could be due to non specific effects of this drug, such as an inhibition of oxygen free radical-dependent reperfusion injury (Westlin & Mullane, 1988;Chopra et al, 1992) and/or an interference with arachidonic acid metabolism (Van Gilst et al, 1987). However, in some experimental models of ischaemia, acute administration of non sulphydryl-containing ACEIs also limited infarct size in rats (Hock et al, 1985) and in cats (Lefer & Peck, 1984). Differences in animal models, duration and severity of ischaemia, occurrence of reperfusion, and drug concentrations could contribute to these conflicting results.…”

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confidence: 99%

Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs

Richard

Ghaleh²,

Berdeaux³

et al. 1993

British J Pharmacology

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1 In order to determine whether the renin-angiotensin system is involved in myocardial ischaemiareperfusion injury, we investigated and compared the effects on infarct size of two different drugs which interfere with this system, i.e., an angiotensin II (AT,) antagonist, EXP3 174, and an angiotensin I-converting enzyme inhibitor (ACEI), enalaprilat in a canine model of ischaemia-reperfusion.2 EXP3174 (0.1 mg kg-', i.v. followed by 0.02mg kg-' h-l for 5.5 h) and enalaprilat (0.3 mg kg-', i.v. followed by 0.06 mg kg-' h-' for 5.5 h) were used in doses inducing a similar level of inhibition (87 ± 4 and 91 ± 3%, respectively) of the pressor responses to angiotensin I. Control animals received saline. 3 Infarct size and area at risk were quantified by ex vivo dual coronary perfusion with triphenyltetrazolium chloride and monastral blue dye. Regional myocardial blood flows (ischaemic and nonischaemic, endocardial, epicardial) were assessed by the radioactive microsphere technique. 4 Both EXP3174 and enalaprilat induced a decrease in mean arterial blood pressure. However, non significant changes in regional myocardial blood flows, whether ischaemic or nonischaemic, were observed after administration of either the ACEI or the AT, antagonist. 5 The size of the area at risk was similar in the three groups. By direct comparison, there were no significant differences between infarct sizes in the three groups. Furthermore, there was a close inverse relationship between infarct size and transmural mean collateral blood flow in controls, and none of the treatments altered this correlation. Thus, neither EXP3174 nor enalaprilat limited infarct size. 6 These results indicate that activation of the renin-angiotensin system does not contribute to myocyte death in this canine ischaemia/reperfusion model.

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“…Other results, however, have been overwhelmingly negative. For (Hock et al, 1985). ACE inhibitors by definition block the conversion of angiotensin I to angiotensin II; thus, reducing the concentration of circulating angiotensin II by ACE inhibition results in systemic and coronary vasodilation (Ertl et al, 1982) and a decrease in vascular resistance (Ertl et al, 1983).…”

mentioning

confidence: 99%

Relationships between structure and effects of ACE inhibitors: comparative effects in myocardial ischaemic/reperfusion injury.

Przyklenk

Kloner

1989

Brit J Clinical Pharma

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1. Coronary artery reperfusion has become the treatment of choice for evolving myocardial infarction. 2. While there is no question that timely restoration of coronary blood flow is essential for the salvage of ischaemic myocardium, coronary reperfusion has also been associated with potentially deleterious consequences. Specifically, the viable tissue salvaged by reperfusion remains ‘stunned’‐i.e., exhibits prolonged abnormalities in contractile function‐for hours to days following reflow. Furthermore, it has been suggested that reperfusion per se may lethally injure some myocytes that were only reversibly injured prior to restoration of blood flow. 3. ACE inhibitors such as captopril and enalapril have been shown to reduce indices of myocardial injury (infarct size, creatine kinase release) and enhance contractile function of stunned myocardium in experimental models of coronary occlusion followed by reperfusion. These effects of ACE inhibitors have largely been attributed to the reduction in myocardial O2‐demand and increase in myocardial blood flow associated with blunting of angiotensin II formation. 4. Recent studies suggest that the effects of some ACE inhibitors‐particularly captopril‐may not solely be explained on the basis of ACE inhibition. In fact, sulphydryl (‐SH) containing ACE inhibitors such as captopril appear to act as scavengers of oxygen‐derived free radical species thought to be important in the pathogenesis of both postischaemic contractile dysfunction and ischaemia/reperfusion induced myocyte necrosis. 5. Thus, ‐SH containing ACE inhibitors‐which both inhibit ACE and scavenge cytotoxic free radicals‐may offer a suitable form of treatment for myocardial ischaemia/reperfusion injury.

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Preservation of ischemic myocardium by a new converting enzyme inhibitor, enalaprilic acid, in acute myocardial infarction

Cited by 90 publications

References 14 publications

Trilinolein Reduces Infarct Size and Suppresses Ventricular Arrhythmias in Rats Subjected to Coronary Ligation

Trilinolein Reduces Infarct Size and Suppresses Ventricular Arrhythmias in Rats Subjected to Coronary Ligation

Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs

Relationships between structure and effects of ACE inhibitors: comparative effects in myocardial ischaemic/reperfusion injury.

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